DESCRIPTION: This project is aimed in part at developing novel compounds that can bind to peptides, proteins, and nucleic acids in water solution with specific recognition of their structures. Compounds are being made that are comprised of two or three cage compounds, each of which can bind an amino acid sidechain, along with other units to interact with charged groups. Selective binders could be direct leads into novel medicinal compounds, since they would block the binding of hormone to receptors, or of proteins to each other. Such binding could have useful biological effects in many diseases: the binding of peptides to their receptors or of proteins to each other in dimers or aggregates are important aspects of many biological processes, including undesirable ones. Selective binding of particular sequences of RNA could be useful in blocking the expression of the RNA of disease organisms, such as those of HIV. The second part of the project deals with the invention and study of novel catalysts that imitate enzymes. It furnishes the simple chemistry relevant to understanding biological chemistry, and such understanding is frequently used as a guide in the development of new medicinals. Also, the chemistry performed in Nature is more effective and more selective than has yet been achieved with related non- biological chemistry. The development of selective chemistry that imitates biological chemistry could be of great use in chemical synthesis, including the synthesis of medicinals. Enzymes typically catalyze reactions by binding their substrates, using hydrophobic and other forces, and then catalyzing the specific needed reaction with two or more catalytic groups, either from the protein sidechains or from coenzymes. In this project the binding will be done with readily available cyclodextrins, or with other synthetic cavity molecules, while the catalysis will be done with acid/base groups, with geometric relationships in the catalyst/substrate complexes, and that will help us understand the reason for rapid catalysis by enzymes. It will also help us design useful catalysts. They may prove to be useful medicinals in their own right, replacing or augmenting catalysis by natural enzymes. For this to be possible, it is important that they function in water solution, as they are designed to do.